A histone finds a traveling companion

The H2A.Z histone has a second job, Gardner et al. have discovered. It escorts an inner nuclear membrane (INM) protein into the nucleus.

The yeast INM protein Mps3 belongs to a protein family, the SUN proteins, that positions chromatin within the nucleus during mitosis and meiosis. Mps3 helps maneuver telomeres and DNA segments containing double-stranded breaks close to the INM. But how does Mps3 get to the INM? Researchers had assumed that newly synthesized Mps3 diffuses from the ER into the INM. If so, the protein could also diffuse back out, suggesting that it needs a mechanism to keep it in place. Gardner et al. investigated whether the H2A.Z histone, which binds to Mps3, serves as a tether for the protein.

The team discovered that Mps3 couldn't reach the INM in cells where H2A.Z was absent, suggesting that H2A.Z shepherds Mps3 into the nucleus. Several lines of evidence indicated that H2A.Z performs this task independently of its chromatin-based functions. For example, chromatin-free H2A.Z can still link up with Mps3. On the other hand, Gardner et al. found that, in the presence of a mutant Mps3 unable to bind to H2A.Z, the histone was still incorporated into chromatin and continued to function in transcription, DNA damage repair, and chromosome organization.

Gardner et al. suspect that the two proteins meet in the cytoplasm and travel to the nucleus together, although whether H2A.Z tethers Mps3 in the INM is unclear. The researchers say that histones in other organisms may also serve as INM protein escorts.